Long-Term Therapy Response to Anti–IL-5 Biologics in Severe Asthma—A Real-Life Evaluation

Eger, Katrien; Kroes, Johannes A.; Brinke, Anneke ten; Bel, Elisabeth H.

doi:10.1016/j.jaip.2020.10.010

Cited by 115 publications

(116 citation statements)

References 31 publications

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“…Several reports have focused on simple switching from omalizumab to mepolizumab 29–31 and from mepolizumab to benralizumab 17 , 32 among the three anti-IL-5/IL-5 receptor antibodies 33 and from a biologic to dupilumab. 34 Most of those reports showed the efficacy of switching biologics.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of Switching Biologics for Severe Asthma Patients in Japan: A Single-Center Retrospective Study

Numata¹,

Araya²,

Miyagawa³

et al. 2021

JAA

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Background In Japan, biologic therapy was initiated for patients with severe asthma in 2009. In recent years, four biologics with different mechanisms of action have become available in the clinical setting. However, the efficacy of switching between biologics remains uncertain. Methods To elucidate the efficacy of switching between biologics, 97 patients were enrolled who had received any biologic therapy for severe asthma at Jikei University Hospital, Tokyo, Japan, from July 2009 to December 2020. We retrospectively examined the patient characteristics, biomarkers, pulmonary function test results, selected biologics, and efficacy. Results Thirty-one males and 66 females received any biologics. The mean age was 53.3 years at the initiation of biologic therapy. Initially, 33, 41, 15 and eight patients received omalizumab, mepolizumab, benralizumab, and dupilumab, respectively. Among three representative indicators for biologics administration, the peripheral blood eosinophil count, serum IgE levels and fractional exhaled nitric oxide, 64% of the patients had two indicators, and 28% had three indicators. Thirty-four patients (35%) switched from the initial biologic to another, and the reasons for switching included persistent asthmatic symptoms (n=22), schedule of hospital visits (n=5), and other reasons. Thus, the treatment was effective in 11 patients after switching. In addition, two patients received combination therapy with different biologics. Eighteen patients (19%) interrupted treatment for various reasons. Regardless of whether the biologic was the initial therapy, the overall efficacy of the four biologics was 60% based on the global evaluation of treatment effectiveness. Conclusion Switching between biologics can be a promising option for severe asthma patients in whom treatment with an initial biologic is ineffective.

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Section: Discussionmentioning

confidence: 99%

Effectiveness of Switching Biologics for Severe Asthma Patients in Japan: A Single-Center Retrospective Study

Numata¹,

Araya²,

Miyagawa³

et al. 2021

JAA

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“…Some considered inadequate response to anti-IL5 or IL5R when no reduction of exacerbation rate, no reduction of OCS dosage, no improvement in physical fitness, persistent severe obstruction in pulmonary function testing (PFT), inadequate treatment response according to patient, persistence of high T2 related biomarkers such as FeNO, persistence or even worsening of symptoms or persistence of uncontrolled comorbidities such as chronic rhinosinusitis or nasal polyps. 12 , 13 Others considered sub-optimal response defined as failing to achieve either ⩾50% reduction in OCS dose, ⩾50% reduction in annualized exacerbation rate (AER), and an ongoing requirement of ⩾7.5 mg prednisolone/day or an AER of ⩾3. 14 The strength of our study is to base the notion of treatment failure on a robust definition established by consensus from an expert panel with appropriate knowledge of the issue.…”

Section: Discussionmentioning

confidence: 99%

Anti-interleukin 5 therapies failure criteria in severe asthma: a Delphi-consensus study

Mattei

Suehs

Alagha

et al. 2021

Ther Adv Respir Dis

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Background: Current practices for assessing response to anti-interleukin 5/R treatment in severe asthma patients are heterogeneous. The objective of this study was to achieve an expert consensus defining failure criteria for anti-interleukin 5/R treatment in severe asthma patients. Methods: Experts were invited to a 5-round Delphi exercise if they were pulmonologists managing ⩾30 patients at a nationally recognized severe asthma expert centre. Following two rounds of statement-generating brainstorming, the expert panel ranked each statement according to a 5-point Likert-type scale during three additional rounds. Positive consensus was considered achieved when ⩾80% of experts agreed with a statement with >50% strong agreement and <15% disagreement. Results: Twenty experts participated in the study. All experts agreed that predefined treatment goals defining effectiveness should be personalized during shared decision making via a patient contract. Treatment failure was defined as (1) absence of a reduction in exacerbation rates by ⩾25% or (2) absence of a reduction in oral corticosteroid therapy by ⩾25% of the initial dosage or (3) occurrence of emergency room visits or hospitalizations after 6 months of treatment. Treatment failure should result in discontinuation. For partial responders, treatment discontinuation was not recommended unless an alternative from another therapeutic class exists and should be discussed in a multidisciplinary consultation. Conclusion: The present study provides objective criteria for anti IL5 or IL5R failure in severe asthma and suggests consensus based guidelines for prescription, evaluation and discontinuation decision-making.

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“…A double‐centre study that included severe eosinophilic asthma patients under treatment with anti‐IL5/IL5R mAbs, assessed the prevalence of “super‐responders,” “partial‐responders” and “non‐responders” in a long‐term period. 59 “Super‐responders,” “partial‐responders” and “non‐responders” were defined according to the OCS assumption, ACQ score, FEV1% of predicted levels, FeNO levels and comorbidities control. Non‐responders were 11% of the total number ( n = 114) and were considered those who reported clinical worsening with either increased symptoms, decreased FEV1, or increased OCS use.…”

Section: Predictors Of Poor Responsementioning

confidence: 99%

“…A double-centre study that included severe eosinophilic asthma patients under treatment with anti-IL5/IL5R mAbs, assessed the prevalence of "super-responders," "partial-responders" and "non-responders" in a long-term period. 59 "Super-responders,"…”

Section: Pred I C Tor S Of P Oor Re S P On S Ementioning

confidence: 99%

Treating severe asthma: Targeting the IL‐5 pathway

Principe

Porsbjerg

Ditlev

et al. 2021

Clin Experimental Allergy

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Severe asthma is a heterogeneous disease with different phenotypes based on clinical, functional or inflammatory parameters. In particular, the eosinophilic phenotype is associated with type 2 inflammation and increased levels of interleukin (IL)‐4, IL‐5 and IL‐13). Monoclonal antibodies that target the eosinophilic inflammatory pathways (IL‐5R and IL‐5), namely mepolizumab, reslizumab, and benralizumab, are effective and safe for severe eosinophilic asthma. Eosinophils threshold represents the most indicative biomarker for response to treatment with all three monoclonal antibodies. Improvement in asthma symptoms scores, lung function, the number of exacerbations, history of late‐onset asthma, chronic rhinosinusitis with nasal polyposis, low oral corticosteroids use and low body mass index represent predictive clinical markers of response. Novel Omics studies are emerging with proteomics data and exhaled breath analyses. These may prove useful as biomarkers of response and non‐response biologics. Moreover, future biomarker studies need to be undertaken in paediatric patients affected by severe asthma. The choice of appropriate biologic therapy for severe asthma remains challenging. The importance of finding biomarkers that can predict response continuous an open issue that needs to be further explored. This review describes the clinical effects of targeting the IL‐5 pathway in severe asthma in adult and paediatric patients, focusing on predictors of response and non‐response.

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Long-Term Therapy Response to Anti–IL-5 Biologics in Severe Asthma—A Real-Life Evaluation

Cited by 115 publications

References 31 publications

Effectiveness of Switching Biologics for Severe Asthma Patients in Japan: A Single-Center Retrospective Study

Effectiveness of Switching Biologics for Severe Asthma Patients in Japan: A Single-Center Retrospective Study

Anti-interleukin 5 therapies failure criteria in severe asthma: a Delphi-consensus study

Treating severe asthma: Targeting the IL‐5 pathway

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